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Journal of Virology, July 2002, p. 6460-6472, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6460-6472.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Human Monocytic Cell Lines Transformed In Vitro by Epstein-Barr Virus Display a Type II Latency and LMP-1-Dependent Proliferation

Eric Masy,1,2 Eric Adriaenssens,1 Claire Montpellier,3 Pascale Crépieux,1 Alexandra Mougel,1 Brigitte Quatannens,3 Gautier Goormachtigh,1 Nathalie Faumont,4 Fabienne Meggetto,4 Claude Auriault,1 Hervé Groux,5 and Jean Coll1*

UMR 8527,1 UMR 8526, CNRS/LilleII/Institut Pasteur de Lille, Institut de Biologie de Lille, Lille,3 Service de Biologie Clinique, Centre Hospitalier, Valenciennes Cedex,2 UPR 2163 CNRS, Centre Hospitalier Universitaire Purpan, Toulouse,4 INSERM U343, Hôpital de l'Archet, Nice, France5

Received 25 September 2001/ Accepted 27 March 2002

Epstein-Barr virus (EBV) classically infects and transforms B lymphocytes in vitro, yielding lymphoblastoid cell lines (LCLs). In contrast to other herpesviruses, EBV is not described as an infectious agent for monocytes. However, recent papers described in vitro infection of monocytes leading to abortive or transient viral expression. In the present study, we report the characterization of E1, a monocytic cell line infected and transformed by EBV. This cell line was derived from an LCL by a drastic electroporation and selection of neomycin-resistant cells, unfavorable to B-cell outgrowth. E1 expressed surface molecules of monocytic lineage (CD14, major histocompatibility complex class II, and CD80) and the c-fms gene, a highly specific marker for the monocytic lineage. This cell line is able to phagocytose and secrete proinflammatory monokines tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8. E1 cells are tumorigenic after injection in nude mice, and a monocytic cell line obtained from one of these tumors (TE1) displayed immunophenotype and functional properties similar to those of E1. We detected the presence of the EBV genome in both cell lines, as well as expression of the EBNA-1 and LMP-1, but not EBNA-2, viral genes, characteristic of a type II latency. LMP-1 influences the phenotype of these monocytic cell lines, as demonstrated by down-regulation of cell proliferation and membrane intercellular adhesion molecule 1 expression due to an LMP-1 antisense strategy. This is the first description of a latently infected human monocytic cell line and the first direct demonstration of an instrumental role for LMP-1 in the proliferation of EBV-transformed cell lines expressing a type II latency.

* Corresponding author. Mailing address: UMR 8527, CNRS/LilleII/Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue Calmette, 59021 Lille Cedex, France. Phone: 33-320871234. Fax: 33-320871233. E-mail: Jean.Coll{at}ibl.fr.

Journal of Virology, July 2002, p. 6460-6472, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6460-6472.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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